Adrenal Androgen Biosynthesis with Special Attention to P450c17 a

Adrenal Androgen Biosynthesis with Special Attention to P450c17 a
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肾上腺雄激素生物合成,特别关注 P450c17 a

DOI:
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发表时间:
1995
影响因子:
5.2
通讯作者:
W. Rainey
W. Rainey
中科院分区:
综合性期刊3区
文献类型:
--
作者:
J. Mason;I. Bird;W. Rainey

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由于获取肾上腺的困难,人肾上腺雄激素合成的体外研究受到限制。我们描述了使用人类肾上腺皮质肿瘤H295细胞系作为模型来评估控制c19类固醇产生的机制。通过类固醇分泌和17 α -羟化酶细胞色素P450 (P450c17)表达的诱导来测定细胞对多种药物的反应性,P450c17是c19类固醇产生的关键酶。福斯克林和二丁基cAMP比ACTH更有效,在48小时的治疗期间增强了脱氢表雄酮和雄烯二酮的产生。通过增加细胞内钙(血管紧张素II和K+离子)以及蛋白激酶A途径激活剂(ACTH, forskolin和二丁基cAMP)的作用的药物分别增加了P450c17的mRNA水平和活性。此外,血管紧张素II而不是K+离子减弱了由激酶A激动剂促进的增加的表达。因此,人类肾上腺P450c17通过多种信号通路表达的复杂性可能对人类肾上腺皮质类固醇形成的多种模式起重要作用。
In vitro studies of human adrenal androgen synthesis are limited because of the difficulties in obtaining adrenals. We describe the use of the human adrenocortical tumor H295 cell line as a model to evaluate mechanisms controlling C19-steroid production. The cells were characterized with regard to responsiveness to a variety of agents as measured by steroid secretion and induction of 17 alpha-hydroxylase cytochrome P450 (P450c17) expression, a key enzyme in C19-steroid production. Forskolin and dibutyryl cAMP, which were more effective than ACTH, enhanced the production of DHEA and androstenedione over a 48-hour treatment period. Agents that act by increasing intracellular calcium (angiotensin II and K+ ions) as well as protein kinase A pathway activators (ACTH, forskolin, and dibutyryl cAMP) individually increased the mRNA levels and activity of P450c17. In addition, angiotensin II but not K+ ions attenuated the increased expression promoted by the kinase A agonists. Thus, the complexity of human adrenal P450c17 expression through multiple signaling pathways may contribute importantly to the diverse patterns of human adrenocortical steroidogenesis.
佛波酯对培养的人胎儿肾上腺细胞中类固醇生成的作用。
DOI: 10.3109/07435808609035450
发表时间: 1986
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影响因子: 2.1
作者:
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DOI: --
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DOI: 10.1210/endo.132.2.8381079
发表时间: 1993
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影响因子: 4.8
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DOI: 10.1210/jcem.77.3.8396576
发表时间: 1993
期刊: The Journal of clinical endocrinology and metabolism
影响因子: --
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